Mechanisms of inhibition of advanced glycation product (AGE) and α-glucosidase by Heliotropium bacciferum: Spectroscopic and molecular docking analysis

Moneera Saud Al-Bagmi; Majed S Alokail; Amal M Alenad; Abdullah M Alnaami; Abuelgassim O Abuelgassim; Mohd Shahnawaz Khan

doi:10.1016/j.ijbiomac.2024.131609

Mechanisms of inhibition of advanced glycation product (AGE) and α-glucosidase by Heliotropium bacciferum: Spectroscopic and molecular docking analysis

Int J Biol Macromol. 2024 Apr 13:131609. doi: 10.1016/j.ijbiomac.2024.131609. Online ahead of print.

Authors

Moneera Saud Al-Bagmi¹, Majed S Alokail¹, Amal M Alenad², Abdullah M Alnaami³, Abuelgassim O Abuelgassim², Mohd Shahnawaz Khan⁴

Affiliations

¹ Protein Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
² Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
³ Chair for Biomarkers of Chronic Diseases, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
⁴ Protein Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia. Electronic address: moskhan@ksu.edu.sa.

PMID: 38621555
DOI: 10.1016/j.ijbiomac.2024.131609

Abstract

Diabetes mellitus is characterized by hyperglycemia that makes insulin more prone to glycation and form advanced glycation end products (AGEs). Here, we report the effect of glyoxal (GO) on the formation of AGEs using human insulin as model protein and their structural modifications. The present investigation also reports the anti-AGE potential of Heliotropium bacciferum (Leaf) extracts. The phytochemical analysis of H. bacciferum revealed that free phenolic extract contains higher amount of total phenolic (3901.58 ± 17.06 mg GAE/100 g) and total flavonoid content (30.41 ± 0.32 mg QE/100 g) when compared to bound phenolic extract. Naringin and caffeic acid were identified as the major phenolic ingredients by UPLC-PAD method. Furthermore, bound phenolics extract showed significantly higher DPPH and superoxide radicals scavenging activity (IC₅₀ 17.53 ± 0.36 μg/mL and 0.306 ± 0.038 mg/ mL, respectively) (p ≤ 0.05). Besides, the bound phenolics extract also showed significant (p ≤ 0.05) chelating power (IC₅₀ 0.063) compared to free phenolic extract. In addition, bound phenolic extract could efficiently trap GO under physiological conditions. Spectroscopic investigation of GO-modified insulin illustrated changes in the tertiary structure of insulin and formation of AGEs. On the other hand, no significant alteration in secondary structure was observed by far UV-CD measurement. Furthermore, H. bacciferum extract inhibited α-glucosidase activity and AGEs formation implicated in diabetes. Molecular docking analysis depicted that GO bind with human insulin in both chains and forms a stable complex with TYR A: 14, LEU A:13, ASN B:3, SER A:12 amino acid residues with binding energy of - 2.53 kcal/mol. However, caffeic acid binds to ASN A:18 and GLU A:17 residues of insulin with lower binding energy of -4.67 kcal/mol, suggesting its higher affinity towards human insulin compared to GO. Our finding showed promising activity of H. bacciferum against AGEs and its complications. The major phenolics like caffeic acid, naringin and their derivatives could be exploited for the drug development for management of AGEs in diabetes.

Keywords: Advanced glycation end products (AGEs); DPPH; Heliotropium bacciferum; Human insulin; Metal chelating; Molecular docking; Phenolic compounds; Superoxide; α-Glucosidase.